Despite recent advances in the composition of chylomicrons and very low density lipoproteins (VLDL), little is known concerning the importance of specific apoprotein constituents in normal and altered states of intestinal lipoprotein production. The increasing awareness that the intestine is an active site of lipoprotein production and may contribute to the pathogenesis of various hyperlipidemias, makes an understanding of intestinal lipoprotein formation of potential importance. We therefore propose to study lymph lipoprotein formation and apoprotein synthesis during various conditions of lipid feeding to better define the importance of these apoproteins in intestinal lipoprotein formation. The mesenteric lymph fistula rat will be used for these studies. Individual chylomicron and VLDL apoproteins (apo B, A1, argenine rich apoproteins) will be purified from mesenteric lipoproteins and monospecific antisera developed. These antisera will be used to quantitate the apoprotein content of mesenteric lipoproteins and intestinal mucosa during conditions of high feeding and cholesterol feeding. Changes in chylomicron and VLDL apoprotein composition will be correlated with studies of apoprotein synthesis. Localization of chylomicron apoproteins within rat intestinal epithelium will be carried out using fluorescent antibody techniques on isolated intestinal cells. These studies will permit correlations to be made between lymph chylomicron apoprotein synthesis and the mucosal content of apoproteins during various experimental conditions of lipid feeding. Using similar techniques, apoprotein localization (apo B, AI) will be carried out on human intestinal biopsies during lipid feeding and in patients with abetalipoproteinemia. These studies should provide insight into the importance of specific apoproteins in intestinal lipoprotein formation.